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. 2016 Mar 11;17(3):363. doi: 10.3390/ijms17030363

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© 2016 by the authors; licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).

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Schematic representation of argininosuccinate synthetase (ASS)-negative cell death induced by arginine deprivation. In ASS-negative cells, arginine cannot synthesize so arginine depletion by ADI or arginase would induce a quick response of cell autophagy by the mammalian Target of Rapamycin (mTOR) or MEK-ERK pathway. Autophagy could recycle limited arginine and prevent apoptosis as a survival response in the short term. Instead, in long-term arginine deprivation, autophagy would contribute to caspase-independent (CASP-IND) cell death and caspase dependent (CASP-DEP) apoptosis could also happen. The dashed lines ( and ) means the reactions are dependent on the availability of enzymes (panel A) or the reactions have not yet confirmed by experiments (panel B). MEK: mitogen-activated protein kinase, also known as extracellular signal-regulated kinase kinase; ERK: extracellular signal-regulated kinase.

Inline graphic — Schematic representation of argininosuccinate synthetase (ASS)-negative cell death induced by arginine deprivation. In ASS-negative cells, arginine cannot synthesize so arginine depletion by ADI or arginase would induce a quick response of cell autophagy by the mammalian Target of Rapamycin (mTOR) or MEK-ERK pathway. Autophagy could recycle limited arginine and prevent apoptosis as a survival response in the short term. Instead, in long-term arginine deprivation, autophagy would contribute to caspase-independent (CASP-IND) cell death and caspase dependent (CASP-DEP) apoptosis could also happen. The dashed lines ( and ) means the reactions are dependent on the availability of enzymes (panel A) or the reactions have not yet confirmed by experiments (panel B). MEK: mitogen-activated protein kinase, also known as extracellular signal-regulated kinase kinase; ERK: extracellular signal-regulated kinase.